Only 8 spots left

~8 spots leftby Dec 2027

Alvelestat for Bronchiolitis Obliterans Syndrome

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen bySteven Z Pavletic, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Inhaled steroids, Montelukast

Must not be taking: Neutrophil elastase inhibitors

Disqualifiers: Pregnancy, Significant alcohol use, others

No Placebo Group

Trial Summary

What is the purpose of this trial?Background: Bronchiolitis obliterans syndrome (BOS) is a complication people can experience after hematopoietic stem cell transplant. It usually affects people with chronic graft versus host disease (cGVHD). This occurs when donor stem cells attack the cells of the person who received them. BOS reduces airflow and oxygen levels in the body. It may be caused by neutrophil elastase in the body. Researchers believe the new drug alvelestat (MPH966) may help. Objectives: To test the safety of alvelestat (MPH966) and see what dose best inhibits neutrophil elastase in people with BOS after a stem cell transplant. To study how well the best dose improves lung function in those people. Eligibility: Adults 18 and older who have had a hematopoietic stem cell transplant and have cGVHD and BOS. Design: Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have lung function and heart function tests. They will have computed tomography scans of the chest. Study part 1: Participants will take the starting dose of the study drug by mouth twice a day for 14 days. This is 1 cycle. They will get different doses, for up to 4 cycles. Study part 2: Participants will take the study drug twice a day by mouth at the dose set in part 1, for up to 12 months. Participants will keep medicine diaries. Participants will have several study visits. These may include: Repeats of the screening tests. Bronchoscopy with bronchoalveolar lavage. Sputum samples taken. 6-minute walking test. cGVHD assessment and answer questions. Participants will be contacted after the study for up to 24 months.

Do I need to stop taking my current medications to join the trial?

The trial does not specify that you must stop taking all current medications, but if you are on azithromycin, you need to stop it at least 2 weeks before joining. If you are on systemic therapy for cGVHD, you must be on stable or tapering doses for the previous 4 weeks.

Eligibility Criteria

Adults over 18 who've had a stem cell transplant and suffer from chronic graft versus host disease (cGVHD) with Bronchiolitis Obliterans Syndrome (BOS). They must have been treated for cGVHD, have certain lung function test results, stable organ/marrow function, and agree to contraception. Excluded are those with recent malignancy treatments, uncontrolled illnesses, pregnancy/breastfeeding, prior neutrophil elastase inhibitors use or significant alcohol consumption.

Inclusion Criteria

I have chronic GVHD and BOS after my stem cell transplant.

I have been on a specific treatment for at least 3 months before joining.

I was diagnosed with BOS within the last 5 years for Phase 2, or any time for Phase 1b.

+8 more

Exclusion Criteria

I have non-alcoholic fatty liver disease or have been on related medication for over 2 weeks in the last year.

I have not had any serious illnesses in the last month.

I have used neutrophil elastase inhibitors before.

+7 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1b Treatment

Participants receive escalating doses of alvelestat (MPH966) to determine the optimal biologic dose and safety over 8 weeks

8 weeks

Weekly visits for dose escalation

Phase 2 Treatment

Participants receive alvelestat (MPH966) at the optimal biologic dose for up to 6 months to assess efficacy

6 months

Monthly visits for efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Periodic contact for follow-up

Optional Continuation

Participants with stable or responding disease may continue therapy for an additional 6 months

6 months

Participant Groups

The trial is testing alvelestat (MPH966), which may inhibit neutrophil elastase that's thought to contribute to BOS after stem cell transplants. It involves two parts: varying doses over cycles up to 4 months followed by the best dose for up to a year. Participants will undergo extensive monitoring including lung/heart tests and bronchoscopy.

2Treatment groups

Experimental Treatment

Group I: Phase 2Experimental Treatment1 Intervention

MTD po bid on days 1-28

Group II: Phase 1bExperimental Treatment1 Intervention

Phase Ib dose escalation